Summary: The histone H3 mutations found recently found in cancers have dramatic downstream effects on the landscape of the epigenome ? chromatin state and DNA methylation ? with eventual secondary outcomes manifested in gene expression and cellular phenotypes. Modern functional genomics approaches provide invaluable tools to study the effects of this epigenome-mediated cascade. In this Core activity, we will establish a set of genomics tools and computation methods to elucidate the mechanisms through which H3 variants impact the epigenome, transcriptome, and finally the cell during neoplastic transformation.